title: Hydrogen sulfide is an endogenous regulator of aging in Caenorhabditis elegans.
abstract: OBJECTIVE
  To investigate the role of endogenous hydrogen sulfide (H2S) in the control of aging and healthspan of Caenorhabditis elegans.
  
  
  RESULTS
  We show that the model organism, C. elegans, synthesizes H2S. Three H2S-synthesizing enzymes are present in C. elegans, namely cystathionine γ lyase (CSE), cystathionine β synthetase, and 3-mercaptopyruvate transferase (MPST or 3-MST). Genetic deficiency of mpst-1 (3-MST orthologue 1), but not cth-2 (CSE orthologue), reduced the lifespan of C. elegans. This effect was reversed by a pharmacological H2S donor (GYY4137). GYY4137 also reduced detrimental age-dependent changes in a range of physiological indices, including pharyngeal contraction and defecation. Treatment of C. elegans with GYY4137 increased the expression of several age-related, stress response, and antioxidant genes, whereas MitoSOX Red fluorescence, indicative of reactive oxygen species generation, was increased in mpst-1 knockouts and decreased by GYY4137 treatment. GYY4137 additionally increased the lifespan in short-lived mev-1 mutants with elevated oxidative stress and protected wild-type C. elegans against paraquat poisoning. The lifespan-prolonging and health-promoting effects of H2S in C. elegans are likely due to the antioxidant action of this highly cell-permeable gas.
  
  
  METHODS
  The possibility that novel pharmacological agents based on the principle of H2S donation may be able to retard the onset of age-related disease by slowing the aging process warrants further study.
  
  
  CONCLUSIONS
  Our results show that H2S is an endogenous regulator of oxidative damage, metabolism, and aging in C. elegans and provide new insight into the mechanisms, which control aging in this model organism.
authors.affiliation: 1 School of Biomedical Science, King's College London, London, United Kingdom .
authors.forename: Bedoor
authors.initials: B
authors.lastname: Qabazard
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Jan
authors.initials: J
authors.lastname: Gruber
authors.forename: Meng Teng
authors.initials: MT
authors.lastname: Peh
authors.forename: Li Fang
authors.initials: LF
authors.lastname: Ng
authors.forename: Srinivasan Dinesh
authors.initials: SD
authors.lastname: Kumar
authors.forename: Peter
authors.initials: P
authors.lastname: Rose
authors.forename: Choon-Hong
authors.initials: CH
authors.lastname: Tan
authors.forename: Brian W
authors.initials: BW
authors.lastname: Dymock
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Swain
authors.forename: Barry
authors.initials: B
authors.lastname: Halliwell
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Stürzenbaum
authors.forename: Philip K
authors.initials: PK
authors.lastname: Moore
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009946:Organothiophosphorus Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: C529376:GYY 4137; D009025:Morpholines; D009946:Organothiophosphorus Compounds; D006862:Hydrogen Sulfide